Moving Closer to Isolating Neurocognitive Mechanisms of Resilience to Anxiety in Youth With Early Childhood Adversity.

Early childhood adversity linked to parenting is associated with an increased lifetime risk for numerous mental health disorders (1,2). Over the last decade, seminal longitudinal research has demonstrated that lasting effects of these adverse childhood experiences on brain function can diminish or exacerbate this risk (3–5). In this issue of Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Callaghan et al. (6) begin to answer a critical question: how do early caregiving experiences “get under the skin” to exert long-term effects on the relation between brain function and symptoms of psychopathology? In this case, the authors focus on anxiety. To do so, they build on established rodent literature demonstrating that when exposed to stress in the presence of a parental cue, young pups that have experienced high-quality parenting relative to low-quality parenting exhibit diminished behavioral signs of distress, decreased stress hormone release, and blunted amygdala response (7). Critically, this parental “buffering” effect on amygdala function is absent in older pups (8). Thus, childhood may be a sensitive period during which the effects of highquality parenting in infancy shape lasting neurobiological responses to stressors, and whereby the absence of such shaping caused by low-quality parenting may contribute to heightened amygdala reactivity often associated with anxietylike behavior. In children, Callaghan et al. (6) describe these relations as a neuroenvironmental loop and hypothesize that early parental care, brain development, and behavior interact to scaffold the maturation of emotion regulation circuitry. Callaghan et al. (6) made important inroads in testing this hypothesis by pairing neuroimaging with the longitudinal assessment of symptoms of anxiety across 3 years in a unique sample of youths (n = 102) who experienced early childhood adversity linked to caregiving (adoption after previous institutionalization [PI]) and those who had been reared from birth by their biological parents. During either childhood or adolescence, youths underwent functional magnetic resonance imaging while viewing photographs of their own parent or a stranger. Buffering was defined as a decrease in right amygdala response to viewing one’s own parent relative to a stranger. Overall, children without early childhood adversity exhibited diminished amygdala responses, whereas PI children and adolescents from both rearing groups did not. However, a substantial number of youths in both rearing groups exhibited decreased amygdala reactivity. In a test of their neuroenvironmental loop hypothesis, Callaghan et al. (6) then demonstrated that early childhood adversity interacted with brain function to influence the expression of anxiety symptoms